Soft corals belonging to the genus Xenia are a rich source of diterpenoids. Diterpenoids are secondary metabolites containing as their most characteristic and unique feature a nine-membered monocarbocyclic ring. The structures of Xenia diterpenoids have been divided into three groups: xenicins (containing a dihydropyran-cyclononane skeleton), xeniolides (possessing a δ-lactone-cyclononane skeleton), and xeniaphyllanes (with a bicyclo[7.2.0]undecane skeleton). 1,2-xenicanes combine unique structural features with interesting biological activities, specifically they are cytotoxic against several human cancer cell lines.
A major limitation in the study of natural products from marine invertebrates, especially diterpenes, has been the difficulty in obtaining these compounds in sufficient quantities. First, attempting to re-isolate reasonable amounts of the same compound from the organism is difficult given the changing natural growth environment of these organisms. Second, the framework of nine-membered rings and the particular arrangement of functional groups with multiple embedded stereocenters limit the range of chemical reactions that are applicable to their synthesis. There is little in the existing synthetic literature to define an effective strategy for the synthesis of xenicanes.
Screening of organic extracts of marine algae and cyanobacteria for mechanism-based anticancer agents has been quite productive and has led to the discovery of new chemotypes showing antiproliferative properties. Cytotoxic chemotherapeutics currently in use rely on the ability to selectively target proliferating cells, which are enriched in tumors. Unfortunately, these drugs are also cytotoxic to proliferating normal cells, accounting for the severe and potentially lethal side effects that limit dosing and effectiveness. Moreover, while sometimes effective, cytotoxic chemotherapy non-specifically damages both normal and tumor cells, with successful treatment often relying on preferential induction of cell death by apoptosis in tumor cells. Tumor cells, however, evolve apoptosis-resistance mechanisms that confound treatment necessitating the development of the therapeutic means for restoring the capacity for apoptosis in cancers. While many conventional cytotoxic chemotherapeutics trigger apoptosis indirectly by inflicting cellular damage, recent efforts have evolved to develop agents that specifically target or activate the apoptotic pathway.